Orbitofrontal sulcogyral morphology: its distribution, structural and functional associations, and predictive value in different diagnostic groups

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Mcintosh, Andrew

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Chakirova, Goultchira

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2013-11-08T15:59:01Z

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2013-11-08T15:59:01Z

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2013-07-06

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http://hdl.handle.net/1842/8098

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Bipolar affective disorder and schizophrenia are highly heritable psychiatric
illnesses and the leading causes of worldwide disability. The orbitofrontal
cortex (OFC) is a region of the frontal lobe with wide spread connectivity with
other brain areas involved in reward, motivation and emotion. Evidence from
various neuroimaging, genetic, post-mortem and brain lesion studies suggest that orbitofrontal cortex may play a role in pathophysiology of mental
illnesses.
This thesis sought to investigate the pathogenesis of major psychiatric
illnesses through the investigation of orbitofrontal morphology in
schizophrenia and bipolar disorder and through its associations with brain
structure and function. Orbitofrontal morphology and its structural and
functional associations were examined in healthy controls, patients with
schizophrenia or bipolar affective disorder, and those at high genetic risk
using functional and structural MRI.
In the first study we found that the orbitofrontal type III is more frequent and
the orbitofrontal type I is less common in the right hemisphere in patients with
schizophrenia while in patients with bipolar disorder type III appears more
often in both left and right hemispheres. We then sought to examine the
relationship of orbitofrontal morphology to disease risk in a study of 146
people at high risk of developing schizophrenia and 110 people at high risk of
developing bipolar disorder. We discovered that in the unaffected high risk
groups the orbitofrontal type III predicted the development of later psychiatric
illnesses, when combined with anterior cingulate morphology. Finally we
showed, in a further study, that OFC morphology was associated with
measures of schizotypy, brain structure, brain function and cognition.
In conclusion, orbitofrontal morphology is linked to major psychiatric disorder
and has significant structural and functional associations. As orbitofrontal
sulcogyral patterns are formed in early life a fuller awareness of their
relevance to brain function holds out the prospect that we could use such
measures as an indicator of vulnerability to the development of illness later in
life. This work points to the potential for the foundation of a theory of
predictive associations between morphological patterns and the development
of psychosis.